Abstract 592
Background
Metastatic colon cancer has a survival rate less than %5 despite the use of effective chemotherapeutic regimen. Prognostic and predictive importance of EGFR is still contradictive in colon cancer. Tyrosine kinase inhibitor canertinib was used in this study to block the EGFR receptor. The effect of Palladium (Pd) (II) compound [PdCl(terpy)](sac).2H2O] and canertinib combination treatment was investigated in this study. 5-fluorouracil (5-FU), a chemotherapeutic drug was used as positive control.
Methods
The cytotoxic effects of the combination of Pd (II)+canertinib and the 5-FU+canertinib combination on colon cancer cell line (HCT-15, HT-29) were determined by the SRB test. Apoptosis, the acidic vesiculations, mitochondrial depolarization were determined by flow cytometry, Annexin-V-Cy3/SYTOX, acridine orange, JC-1 staining. Alterations in proteins related to EGFR-associated pathway, EMT, apoptosis/autophagy and drug carrier were evaluated by western blot. Invasion, wound healing and colony forming ability were determined. Tube forming in HUVEC and vessel forming ability was assessed by matrigel and CAM test respectively.
Results
A significant decrease in p-ERK, p-P38, p-EGFR protein levels was observed with EGFR inhibition, while the cell viability was decreased. Cell death was determined as mitochondrial apoptosis. LC3-II, Beclin-1, Atg5 protein levels, and increased acidic vesicles and decreased p-MTOR protein levels were associated with increased autophagy in combination therapy. In addition, increased E-cadherin expression and decreased N-cadherin, fibronectin and vimentin expression related to decrease in invasion, migration, and colony forming ability. ROS expression and DNA damage increased. Significant differences in MDR-1 and MRP-1 protein levels were observed with EGFR inhibition. In addition, the ability to create tubes and vessels has decreased significantly.
Conclusions
EGFR inhibition along with Pd(II) has been shown to increased cytotoxicity, decreased invasion, migration and vessel formation abilities. Furthermore, induced ROS levels and increased autophagic signaling are found to be necessary for mitochondria-dependent apoptosis in colon cancer cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Uludag University.
Funding
Scientific Research Projects Foundation (BAP) of Uludag University of Turkey [Project No. (DDP(F)-2017)].
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3336 - Survival outcome of non-small cell lung cancer (NSCLC) patients: Comparing results between the database of the Comprehensive Cancer Center Zürich (CCCZ) and the Epidemiological Cancer Registry Zurich and Zug (KKR)
Presenter: Rolf A. Stahel
Session: Poster Display session 1
Resources:
Abstract
2204 - NORA trial (GECP 15/02): Updated results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Presenter: María Guirado
Session: Poster Display session 1
Resources:
Abstract
1446 - A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators set by principle component analysis
Presenter: Bo Cheng
Session: Poster Display session 1
Resources:
Abstract
1788 - Prognostic and predictive value of 18F-PET/CT on the response to treatment in locally advanced non-small cell lung cancer (NSCLC)
Presenter: Cristina Alfaro Autor
Session: Poster Display session 1
Resources:
Abstract
2299 - Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non small cell lung cancer
Presenter: Abdurrahman Işıkdoğan
Session: Poster Display session 1
Resources:
Abstract
4211 - Predicting the first failure pattern in patients with inoperable local advanced non-small cell lung cancer (LA-NSCLC) receiving definitive chemoradiotherapy: Establishment and internal validation of a nomogram based on the clinicopathological factors
Presenter: Xueru Zhu
Session: Poster Display session 1
Resources:
Abstract
1550 - Prognostic impact of neutrophil-to-lymphocyte ratio (NLR) pre and post chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC)
Presenter: Vicente Palomar Abril
Session: Poster Display session 1
Resources:
Abstract
2345 - Meta-analysis evaluating neutropenia incidence with EGFR inhibitors and chemotherapy in patients with NSCLC
Presenter: Bernardo Rapoport
Session: Poster Display session 1
Resources:
Abstract
3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC
Presenter: Yu Miura
Session: Poster Display session 1
Resources:
Abstract
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract